These studies are designed to broaden our knowledge of the physiology of gastric inhibitory polypeptide and determine what contribution it may make to the pathogenesis of diabetes mellitus. We will determine which factors, i.e, insulin secretory reserve, obesity, duration of diabetes, presence of pancreatic glucagon are associated with the GIP excess of diabetes, and whether normalization of glycemia by an artifical endocrine pancreas normalizes GIP secretion to a mixed meal in diabetes. We will determine whether excessive GIP in diabetes and obese nondiabetics may be due to delayed clearance of GIP by infusing exogenous porcine GIP. We will detemine whether the blunted GIP response to oral fat observed by others during hyperglycemia may be due to delayed gastric emptying or impaired clearance of GIP rather than an inhibition of insulin on GIP release. In addition we will examine the effect of specific major nutrients, carbohydrate, fat and protein on GIP secretion at specific sites in the small bowel in healthy subjects. We will continue our evaluation of the role of the autonomic nervous system on GIP secretion by infusing glucose through an intraduodenal tube in healthy subjects during infusions of saline, phentolamine, propranolol and atropine on separate days. Annually, 6000 diabetics are examined at the Mayo Clinic. There has been no difficulty in the past in recruiting patients for study. The proposed studies will be performed in the Clinical Study Unit of the Mayo Clnic. Hormonal radioimmunoassays will be performed in the Gastroenterology Reseach Unit and the Diabetes and Metabolism Research Laboratory.